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Nano-TRAIL: a promising path to cancer therapy
Siri Chandana Gampa1, Sireesha V Garimella1, SanthiLatha Pandrangi2
1Department of Biotechnology, Institute of Science, GITAM (Deemed to be University), Andhra Pradesh 530045, India.
Abstract:
Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand, also called apo-2 ligand (TRAIL/Apo-2L), is a cytokine that triggers apoptosis by binding to TRAIL-R1 (DR4) and TRAIL-R2 (DR5) death receptors. Apoptosis occurs through either the extrinsic or intrinsic pathway. The administration of recombinant human TRAIL (rhTRAIL) or TRAIL-receptor (TRAIL-R) agonists promotes apoptosis preferentially in cancerous cells over normal cells in vitro; this phenomenon has also been observed in clinical studies. The limited efficacy of rhTRAIL in clinical trials could be attributed to drug resistance, short half-life, targeted delivery issues, and off-target toxicities. Nanoparticles are excellent drug and gene delivery systems characterized by improved permeability and retention, increased stability and biocompatibility, and precision targeting. In this review, we discuss resistance mechanisms to TRAIL and methods to overcome TRAIL resistance by using nanoparticle-based formulations developed for the delivery of TRAIL peptides, TRAIL-R agonists, and TRAIL genes to cancer cells. We also discuss combinatorial approaches of chemotherapeutic drugs with TRAIL. These studies demonstrate TRAIL's potential as an anticancer agent.
Insights
Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) shows promise in cancer treatment by inducing apoptosis. Nanoparticle delivery systems can enhance TRAIL
Area of Science:
- Biochemistry and Molecular Biology
- Cancer Biology
- Nanomedicine
Background:
- Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) induces apoptosis in cancer cells via death receptors DR4 and DR5.
- TRAIL demonstrates preferential cancer cell apoptosis in vitro and in clinical studies.
- Clinical efficacy of recombinant human TRAIL (rhTRAIL) is limited by drug resistance, short half-life, and delivery issues.
Purpose of the Study:
- To review TRAIL resistance mechanisms and strategies to overcome them.
- To explore nanoparticle-based formulations for enhanced TRAIL delivery.
- To discuss combinatorial therapies involving TRAIL.
Main Methods:
- Review of existing literature on TRAIL resistance and nanoparticle delivery systems.
- Analysis of studies utilizing nanoparticle formulations for TRAIL peptides, TRAIL-receptor agonists, and TRAIL genes.
- Examination of combinatorial approaches with chemotherapeutic drugs.
Main Results:
- Nanoparticles offer improved drug delivery with enhanced permeability, retention, stability, and targeting.
- Nanoparticle-based TRAIL delivery systems show potential in overcoming resistance mechanisms.
- Combinatorial therapies enhance the anticancer efficacy of TRAIL.
Conclusions:
- Nanoparticle-based delivery systems are crucial for overcoming TRAIL resistance and improving its therapeutic index.
- TRAIL, when delivered via nanoparticles, holds significant potential as an anticancer agent.
- Further research into nanoparticle-formulated TRAIL and combination therapies is warranted.
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